A 4-(1-piperazinyl)benzo[b]thiophene compound represented by Formula (1):
is useful for various medicines such as antipsychotic drugs. Moreover, a 4-(1-piperazinyl)benzo[b]thiophene compound represented by Formula (4):
wherein R1 is a hydrogen atom or a protecting group, is useful as an intermediate for synthesizing the compound represented by Formula (1).
Reference Example 30 and Example 1 of PTL 1 specifically disclose a method for producing a benzo[b]thiophene compound (the reaction scheme shown below). In Reference Example 30, 4-(1-piperazinyl)benzo[b]thiophene is produced by heating under reflux a mixture comprising 14.4 g of 4-bromobenzo[b]thiophene, 29.8 g of anhydrous piperazine, 9.3 g of sodium tert-butoxide, 0.65 g of (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), 0.63 g of tris(dibenzylideneacetone)dipalladium (0), and 250 ml of toluene (step X).

However, the reaction of the step X produces a relatively large amount of by-products that can hardly be separated, and the purity of the compound (4a) is thus inevitably reduced. Moreover, although column purification is performed to increase the purity of the compound (4a), it is very difficult to completely remove by-products, even by column chromatography purification. For this reason, there is a demand for the development of a novel method for producing the compound (4a) with high yield and high purity.
Furthermore, by-products contained in the compound (4a) inevitably reduce the purity of the compound (1) in the subsequent step Y. Since the method described in PTL 1 requires purification by column chromatography to obtain the target compound (1) with high purity, the method is not suitable for the industrial process of mass production. In addition, according to the method, incorporation of by-products that can hardly be separated is inevitable, and high-purity products usable as active pharmaceutical ingredients cannot be produced without purification by column chromatography.